Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
Magnetoencephalography (MEG) studies examining superior temporal gyrus (STG) auditory activity in individuals with Autism Spectrum Disorders (ASD) almost uniformly report abnormalities. For example, in the time-domain, several studies have reported delays in the latency of auditory-evoked response peaks in autism, especially that of the 100 ms (M100) STG auditory response (Gage et al. (2003) Neuroreport., 14:2047-51; Roberts et al. (2010) Autism Res., 3:8-18). Although delayed responses have been hypothesized to contribute to language deficits in ASD, there is no clear mechanistic support for such a relationship (Oram Cardy et al. (2008) Int. J. Psychophysiol., 68:170-5; Roberts et al. (2008) Int. J. Psychophysiol., 68:149-60). Emerging evidence also suggests impairments in auditory oscillatory activity in ASD. Presenting 40 Hz click trains to children with autism and age-matched controls, decreased left-hemisphere 40 Hz steady-state gamma band activity was observed in autism (Wilson et al. (2007) Biol. Psychiatry 62:192-7). Presenting 1000 Hz tones and examining the early STG transient gamma-band response, decreased left and right 40 Hz inter-trial coherence (ITC, also called phase-locking factor) in adults with autism as well as in the parents of children with autism was observed, leading to the argument for a deficit in autism in the ability to time gamma oscillations to external stimuli (Rojas et al. (2008) BMC Psychiatry, 8:66).
It is unknown whether a delayed M100 response and decreased auditory gamma activity reflect a single abnormality or if the two abnormalities are distinct. In addition, previous auditory time-frequency studies have focused exclusively on gamma-range activity (˜30 to 50 Hz). The motivation for this is likely due to (1) the association between inhibitory interneuron processes and gamma activity (Bibbig et al. (2002) J. Neurophysiol., 88:1634-54; Whittington et al. (2000) Int. J. Psychophysiol., 38:315-36), and (2) a hypothesized inhibitory interneuron dysfunction in ASD (Casanova et al. (2002) J. Child Neurol., 17:692-5; Uhlhaaset al. (2007) Biol. Psychiatry, 62:190-1). High frequency activity, however, is not the only, or even the primary, component of auditory evoked responses, and many studies show a coupling of low- and high-frequency activity such that high-frequency abnormalities are likely associated with low-frequency abnormalities (Canolty et al. (2010) Trends Cogn. Sci., 14:506-15; Lakatos et al. (2004) Brain Res. Cogn. Brain Res., 19:1-9). Studies observing low-frequency resting-state abnormalities in ASD also indicate the need to assess oscillatory processes pre- and post-stimulus across a broad range of frequencies in order to fully characterize neural abnormalities in ASD (Cantor et al. (1986) J. Autism Dev. Disord., 16:169-87; Murias et al. (2007) Biol. Psychiatry, 62:270-3).